Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer
Growing clinical evidence for the interaction of the p53 genotype and response to induction chemotherapy in advanced non-small cell lung cancer
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DOI：
10.1016/j.jtcvs.2007.10.072
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发表时间：
2008-05-01
影响因子：
6
通讯作者：
Klepetko, Walter
中科院分区：
文献类型：
--
作者：
Kandioler, Daniela;Stamatis, Georgios;Klepetko, Walter
目的：本研究的目的是建立临床证据，证明p53基因型可以作为顺铂诱导治疗反应的预测指标。方法：在前瞻性II期临床试验中，对接受新辅助化疗的晚期非小细胞肺癌患者进行肿瘤p53基因型分析。对诱导治疗的反应与p53基因型相关，通过完整的直接DNA测序进行评估。患者接受顺铂联合依托泊苷治疗3个周期，同时放化疗1个周期。这三种治疗成分都是通过诱导细胞凋亡来调节其细胞毒性作用，这表明需要完整的p53基因。此外，更新了先前发表的假设发现研究的结果，以证明临床结果的一致性，并总结了当前可用的临床证据。结果：在II期试验中，35例患者在诱导化疗后进行了切除，允许进行病理组织学反应评估。p53突变基因型的存在是诱导化疗耐药的高度指示（P < 0.002）。突变型p53基因型识别无反应的敏感性为94%（71.3-99.9置信区间）。p53基因正常与根治性切除（P < 0.004）和生存优势（P = 0.02）显著相关。结论：这是第二次临床评估显示p53基因型与非小细胞肺癌诱导治疗反应之间的显著关系。我们得出结论，p53基因型应该作为前瞻性随机方案诱导治疗反应的预测标志物进行评估。
Objective: The objective of this study is to establish clinical evidence that the p53 genotype can serve as a predictive marker for response to cisplatin-based induction therapy.Methods: Patients with advanced non-small cell lung cancer who had received neoadjuvant chemotherapy in the context of a prospective phase II trial were analyzed for the p53 genotype of their tumors. Response to induction therapy was then correlated to the p53 genotype as assessed by complete direct DNA sequencing. Patients had received 3 cycles of cisplatin and etoposide, and 1 cycle of simultaneous radiochemotherapy. All 3 treatment components mediate their cytotoxic effect through induction of apoptosis, which is suggested to require an intact p53 gene. In addition, the results from a previously published hypothesis-finding study are updated to demonstrate the consistency of clinical results and summarize currently available clinical evidence.Results: In the phase II trial, 35 patients underwent resection after induction chemotherapy, allowing a pathohistologic response assessment. The presence of a mutant p53 genotype was highly indicative of resistance to induction chemotherapy (P < .002). The sensitivity of a mutant p53 genotype to identify nonresponders was 94% (71.3-99.9 confidence interval). A normal p53 gene was significantly associated with radical resection (P < .004) and survival advantage (P = .02).Conclusion: This is the second clinical evaluation demonstrating a significant relation between p53 genotype and response to induction therapy in non-small cell lung cancer. We conclude that the p53 genotype should be evaluated as a predictive marker for response to induction therapy in prospective randomized protocols.